Interstellar dust (ISD) is the condensed phase of the interstellar medium. In situ data from the Cosmic Dust Analyzer on board the Cassini spacecraft reveal that the Saturnian system is passed by ISD ...grains from our immediate interstellar neighborhood, the local interstellar cloud. We determine the mass distribution of 36 interstellar grains, their elemental composition, and a lower limit for the ISD flux at Saturn. Mass spectra and grain dynamics suggest the presence of magnesium-rich grains of silicate and oxide composition, partly with iron inclusions. Major rock-forming elements (magnesium, silicon, iron, and calcium) are present in cosmic abundances, with only small grain-to-grain variations, but sulfur and carbon are depleted. The ISD grains in the solar neighborhood appear to be homogenized, likely by repeated processing in the interstellar medium.
A beamline for the x-ray free electron laser (XFEL) of SPring-8 Angstrom Compact free electron LAser (SACLA) provides hard x-ray pulses in the range 4.5-19.5 keV. Its optical system in an optics ...hutch delivers a pink beam below 15 keV with either of two double-mirror systems or a monochromatic beam with a double-crystal monochromator. These XFEL beams are used for various types of measurement at experimental stations, e.g. x-ray diffraction, coherent diffraction imaging, x-ray spectroscopy and pump-and-probe measurement. The experimental stations consist of experimental hutches and control stations, and a femtosecond optical laser which is synchronized with XFEL pulses. Photon diagnostics have been performed for measuring radiation parameters in a shot-by-shot manner.
Recently novel Epstein–Barr virus (EBV) lymphoproliferative diseases (LPDs) have been identified in non-immunocompromised hosts, both in Asia and Western countries. These include aggressive T-cell ...and NK-cell LPDs often subsumed under the heading of chronic active Epstein–Barr virus (CAEBV) infection and EBV-driven B-cell LPDs mainly affecting the elderly.
To better define the pathogenesis, classification, and treatment of these disorders, participants from Asia, The Americas, Europe, and Australia presented clinical and experimental data at an international meeting.
The term systemic EBV-positive T-cell LPD, as adopted by the WHO classification, is preferred as a pathological classification over CAEBV (the favored clinical term) for those cases that are clonal. The disease has an aggressive clinical course, but may arise in the background of CAEBV. Hydroa vacciniforme (HV) and HV-like lymphoma represent a spectrum of clonal EBV-positive T-cell LPDs, which have a more protracted clinical course; spontaneous regression may occur in adult life. Severe mosquito bite allergy is a related syndrome usually of NK cell origin. Immune senescence in the elderly is associated with both reactive and neoplastic EBV-driven LPDs, including EBV-positive diffuse large B-cell lymphomas.
The participants proposed an international consortium to facilitate further clinical and biological studies of novel EBV-driven LPDs.
POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and ...biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.
Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. ...However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10
, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.
Engineering ceramics have high stiffness, excellent thermostability, and relatively low density, but their brittleness impedes their use as structural materials. Incorporating carbon nanotubes (CNTs) ...into a brittle ceramic might be expected to provide CNT/ceramic composites with both high toughness and high temperature stability. Until now, however, materials fabrication difficulties have limited research on CNT/ceramic composites. The mechanical failure of CNT/ceramic composites reported previously is primarily attributed to poor CNT-matrix connectivity and severe phase segregation. Here we show that a novel processing approach based on the precursor method can diminish the phase segregation of multi-walled carbon nanotubes (MWCNTs), and render MWCNT/alumina composites highly homogeneous. The MWCNTs used in this study are modified with an acid treatment. Combined with a mechanical interlock induced by the chemically modified MWCNTs, this approach leads to improved mechanical properties. Mechanical measurements reveal that only 0.9 vol% acid-treated MWCNT addition results in 27% and 25% simultaneous increases in bending strength (689.6 ± 29.1 MPa) and fracture toughness (5.90 ± 0.27 MPa m(1/2)), respectively.
Abstract
Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide ...(knottin) that selectively recognizes human integrin αvβ
6
with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer’s safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin α
v
β
6
.
Summary
Background
A predisposition to exacerbations is being recognized as a distinct phenotype with “previous exacerbations” representing the strongest clinical factor associated with future ...exacerbation. Thus, to identify additional novel biomarkers associated with asthma exacerbations, “past exacerbation status” must be included as a confounding factor.
Objective
This study aimed to characterize the clinical and biomarker features associated with asthma exacerbations in severe asthma.
Methods
We evaluated clinical parameters from 105 severe asthmatics yearly for 3 years, as well as their exacerbation status. We classified the subjects into 3 groups: (i) consistent non‐exacerbators (CNE, subjects who did not experience any exacerbation over the 3‐year period); (ii) consistent frequent exacerbators (CFE, subjects with frequent exacerbation, defined as those who had 2 or more exacerbations within 1 year, throughout the 3‐year period); and (iii) intermittent exacerbators (IE). We conducted multivariate analysis for comparisons among the groups for multiple factors, including several Th2‐related biomarkers, in addition to the “past exacerbation status.”
Results
Thirty‐nine subjects were classified as CNE, 15 as CFE, and 51 as IE. Frequent exacerbations in the previous year predicted exacerbations for the following year (P < .001). Among the several Th2‐related biomarkers, only FeNO was associated with exacerbation status. When we analysed the data after the second visit, the impact of FeNO on predicting future exacerbation remained significant, even after considering the exacerbation status during the first year (P < .05).
Conclusions and Clinical Relevance
Measurement of FeNO has a significant potential to predict future asthma exacerbation, which is independent of the “past exacerbation history.”
This paper analyzes politics of food education in Japan where food education has become one of the central motifs of food policy in recent years. It describes the emergence of private enterprise ...institutions that offer credentials for people as “food education experts,” the majority of whom are women. Based on a survey of more than one hundred food education experts, the paper explores motivations of these women and finds that the reasons for the popularity of food education certifications are not so much that women wanted to challenge the dominant food system—as agrofood scholars may have expected or hoped for—but for reasons related more to the gendered career expectations and pressures for women to conform to a culturally-scripted feminine ideal. The paper’s importance beyond Japan lies in the discussion of dynamics and implications of privatization of food education. “Privatization” indicates a shift in the location of control and in what is considered to be “necessary” knowledge about food. Subject to market logic, food education is at risk of becoming an exercise of superficial mastering of “sanitized” information. Furthermore, at the core of privatization of food education is an increasingly pervasive approach to food education that I term “food literacy” approach, based upon a deficiency framework which posits individual knowledge and skills as sole reasons for inappropriate food choices, dietary behaviors, and culinary practices. Not only is the food literacy approach highly individualistic and apolitical, but it also enables and exacerbates the privatization and gendered pressures of food education.
A projectile accelerated by the Hayabusa2 Small Carry-on Impactor successfully produced an artificial impact crater with a final apparent diameter of 14.5 ± 0.8 m on the surface of the near-Earth ...asteroid 162173 Ryugu on April 5, 2019. At the time of cratering, Deployable Camera 3 took clear time-lapse images of the ejecta curtain, an assemblage of ejected particles forming a curtain-like structure emerging from the crater. Focusing on the optical depth of the ejecta curtain and comparing it with a theoretical model, we infer the size of the ejecta particles. As a result, the typical size of the ejecta particles is estimated to be several centimeters to decimeters, although it slightly depends on the assumed size distribution. Since the ejecta particles are expected to come from a depth down to ~1 m, our result suggests that the subsurface layer of Ryugu is composed of relatively small particles compared to the uppermost layer on which we observe many meter-sized boulders. Our result also suggests a deficit of particles of less than ~1 mm in the subsurface layer. These findings will play a key role in revealing the formation and surface evolution process of Ryugu and other small Solar System bodies.
PDF
